A Quantitative Structure Activity Relationship study on a Series of 17 molecules of (benzimidazole compounds) with antimicrobial activity analogues was made using combination of various physicochemical descriptors. (Thermodynamic, electronic and spatial). Several statistical expressions for 2D QSAR & 3D QSAR were developed using stepwise partial least square (PLS) regression analysis and K-Nearest neighboring molecular field analysis (K-NNMFA) respectively. The best Quantitative Structure Activity Relationship models were further cross validated. The study revealed that the alignment independent descriptors contributed positive and path count contributed negatively in 2D-QSAR analysis and Electrostatic descriptor contributed positive and steric descriptor contributed negatively in 3D QSAR analysis. 2DQSAR model developed using partial least square regression approach. Negative logarithmic value of (–PMIC) was taken as dependent variable and T_N_N_4, T_2_C_1, T_T_C_4, T_T_S_7 T_2_C_1, ChiV3, T_O_O_7 was taken as independent varable. The analysis resulted in the following 2D-equation suggest that, BA = [-1.2083 (± 9.17986)] + T_O_O_7 1 [0.152608(± 0.336984)] + T_2_C_1 [0.1510 (± 0.000191822)] + T_T_C_4 [-1.8960 (± 0.504224)] n=11, r2 = 0.9717, q2 = 0.8367, F test = 60.0062, pred_r2 = 0.6547, a lipophillic group, which is less bulkier at Ar, is important for guiding the design of a new molecule.3DQSAR model developed using K-nearest neighbour method (training set =11 and test set = 6). Out of several model were developed. The best model derived by the method have crossvalidated coefficient q2 value is 0.7926, Predict r2 value is 0.8919, k Nearest Neighbor is 2, Degree of freedom = 6. The steric and electrostatic descriptors at the grid points, E_442, S_473, S_135, S_190 plays important role for design of new molecule. QSAR analysis of series of benzimidazole compounds informed that electronegative and less bulky group increases the biological activity
